April 20, 1954
COMMUNICATIONS TO THE EDITOR
2281
were, in fact, found to be. All of our data have been obtained a t Oo, and are summarized in Table I. The above data show that the relative reactivities of primary, secondary and tertiary chlorides in the phenacyl series are 1:0.006 :0.000003. This is a more pronounced change than is encountered in the butyl chloride series, and, in view of the previous argument, appears to provide conclusive evidence that the decrease in reactivity as one goes from primary to secondary to tertiary halides is almost entirely due to a steric effect. The two thousand-fold decrease in reactivity as one goes from the secondary to the tertiary chloride is outstanding, and suggests that the keto chloride rate values illustrate the relative reactivities of primary, secondary and tertiary halides in a reaction going entirely by the S N 2 mechanism better than the usually given butyl chloride rate values. We are now studying more carefully the reaction of t-butyl chloride with sodium iodide to determine if an S N ~mechanism contributes appreciably to its relatively high reactivity. If inductive effects are of little importance, one wonders why phenacyl chloride is as reactive as it is. Several investigators4 have suggested that an approaching nucleophilic group can form a loose bond with the carbon atom of the polarized carbonyl group in the transitional state and thus be in a sterically favorable position for the ensuing nucleophilic attack on the alpha carbon. In chloromethyl p-tolyl sulfone, this cannot happen unless the valence shell of the sulfur is expanded, and an unreactive halide is the result. The unreactivity of this compound provides additional evidence of the minor role played by inductive effects. Studies are underway on solvent and temperature effects and the more accurate determination of ORGANICHALIDE the k values of the slow reactions.
and the steric effect to be the major factor. Phenacyl chloride reacts with iodide ion in acetone 9,000 times more rapidly than does n-butyl chloride. If methyl groups are successively substituted into the phenacyl side chain, the resulting secondary and tertiary halides should still be extremely reactive if inductive effects are the deciding factor, but the reactivity should decrease many fold for each methyl group substituted if steric effects are of major importance. The argument for the first statement, assuming inductive effects to be of major importance, is that the increase in electron density at the reacting carbon atom due to the electron releasing ability of the methyl groups must be insignificant compared to the decrease in electron density due to the adjacent carbonyl group. Otherwise a carbonyl group adjacent to a -CHzCI group would not increase the s N 2 reactivity nine thousand-fold whereas a methyl group in the same position decreases the reactivity ten to twentyfold a t most (methyl versus ethyl halides in various S N reactions). ~ Accordingly, the substitution of methyl groups into the phenacyl side chain should not change the electron density a t the reactiny carbon atom appreciably, and the reactivity should show little change as one progresses from the primary to the secondary to the tertiary keto halides. On the other hand, if steric effects are deciding, the secondary halide should react much more slowly than the primary halide (as happens when one goes from n-butyl chloride to sec-butyl chloride in typical SN2 reactions) and the tertiary halide should be even less reactive. This is the way the reactivities of phenacyl chloride, a-chloroa-chloroisobutyrophenone propiophenone and
TABLE I SECOND-ORDER RATE CONSTANTS FOR IODIDESIN DRY REACTINGWITH SODIUMOR POTASSIUM (4) Priority for this suggestion ACETONE AT 0"" J . Chcnz Soc.. 445 (1938). Compound
T i m e for 50% reaction if solution 0.1 Af in k in liters each r e a c t a n t moles-' hours-'
111 days 0.00375* 5 years < O . 0026' 6 years < O . 0002b 18 min. 33. 6b 50 hours 0.200 11 pears
